Sunday, May 31, 2015

Real Science versus GMO Fantasy Science

My last post showed how the microbiome in our guts could give us Alzheimer’s disease (AD).  That’s pretty straightforward and blindsides pro-GMOers, who’ve been telling us how “Glyphosate targets an enzyme found in plants, but not in humans or pets”—an error they may bitterly regret when current legal proceedings grind to an end.  But we’re still far from knowing enough about brain-gut interactions to be able to nail the precise mechanism.

However, when we look at other routes, there’s a confound—the current state of play in AD studies.  Repeatedly we are told that “AD is mostly genetic”, but in fact “later age of disease onset (≥ 65 years) representing most cases of AD [like 98%, DB] has yet to be explained by a purely genetic model.”  So even for those who do harbor suspect genes, there must be some (probably exogenous) factor that triggers them to express whatever causes AD.

One hypothesis was that AD is triggered by failure to synthesize enough of the neurotransmitter acetylcholine, but treatments based on this theory failed to cure or even substantially delay the progress of Alzheimer’s.  A rival hypothesis claimed that AD resulted from the formation in the brain of amyloid plaques, a common feature of AD patients.  This went through several stages as researchers argued over which form of which protein did what to cause the plaques.  Yet a further hypothesis, nowadays maybe the most popular, saw the plaques as merely part of a process that commenced with a different protein, called tau, which supports the internal structure of nerve cells.  These are just the major hypotheses.  Minor ones include causative agents as diverse as herpes, copper, electromagnetic fields, myelin breakdown and oxidative stress.  After decades of study, there is still no proven effective treatment for AD.

But what the facts about AD reveal most clearly is the difference between Real Science and what GMO advocates regard as science.  Even in literary genres, people regularly refer to “Fantasy AND Science Fiction”, thereby carefully drawing a line between the two.  But that line is blurred by GMOers, who regularly produce a genre that can only be called “Fantasy Science”.  So here’s the distinction between Real Science and Fantasy Science.

In Real Science, nothing is cut and dried; even what seem eternal verities are always subject to challenge.  In the 18th century, Pope confidently proclaimed:
          Nature and nature’s laws lay hid in night.
         God said, “Let Newton be!” and all was light.
In the 20th century, the British poet Sir John Squire answered him:
          It did not last: the devil, shouting "Ho,
          Let Einstein be," restored the status quo.

That’s the norm, and the AD literature just represents the same process, speeded up.  It may take many years or even decades for knotty problems to reach, not a final or permanent solution, but a solution that stands up for the moment, may hold indefinitely, but quite possibly won’t last forever.  No matter.  For now it works.  The huge crazy edifice of science shifts and reshuffles itself, and it may comfort us to pretend we’ve reached some kind of terminus, but we know in our hearts this isn’t true.  It all looks terribly inefficient, but in actual fact it’s more efficient, a better guide to understanding nature, than anything else we’ve found or probably ever will find.

For this reason, people in Real Science take one another in good faith.  When someone writes a paper you think is wrong, you don’t accuse him of being an activist not a scientist, or of producing something called “Junk Science”.  You lay out the evidence for your point of view, and possibly (not necessarily) criticize the evidence for the other.  If you produce only evidence for your own views, nobody demonizes you or even accuses you of “cherry-picking”.  Why should they?  What we are looking for is not THE TRUTH, but the best account of reality we can currently manage.  And the best and perhaps only way of doing this is if I make the strongest case I can for my views, and you do the same for yours, and then all the other people who are interested in what we are arguing about pitch in, and in doing so keep eliciting new data, some of which favors me, some you, until there gets to be a preponderance of evidence one way or another.

Not that it’s easy, or even always polite.  Never forget J.B.S. Haldane’s Four Stages of Acceptance for any new idea in science:
          1. This is worthless nonsense.
          2. This is an interesting, but perverse, point of view.
          3. This is true, but quite unimportant.
          4. I always said so.

Well, the world of GMO Fantasy Science is a very different one.  In this alternative universe, science is neatly divided into two kinds.  There is Sound Science and there is Junk Science.  Most science is Sound Science, and all of it strongly supports all aspects of GMOs.  All science that questions any aspect of GMOs is Junk Science, and if it is not swiftly stamped out by the proponents of Sound Science, heaven only knows what might happen!  So those who produce Junk Science are not only demonized—they’re chain-demonized.

Chain-demonization is a phenomenon not yet (to the best of my knowledge) commented on, but it needs to be, because it is a regular strategy employed by Fantasy Scientists, and it is diametrically opposed to anything Real Scientists would ever dream of doing.  It consists of demonizing, not just the authors of particular papers that have pissed off Fantasy Scientists, but (a) any paper written by a demonized scientist (b) any paper in which a demonized scientist appears as a co-author (c) any paper that cites any paper authored or co-authored by a demonized scientist in its bibliography.  All papers that fall into any one of these categories can summarily dismissed without even attempting to discuss their content, because of course their content is—can only be—Junk Science.

So the Fantasy-Science scenario of Men in White Coats Who Know Everything versus fear-mongering activists paid by those huge, evil, organic-food corporations is just that—a fantasy.  The really shocking thing, though, is that this fantasy is accepted by people who should know better—like so many science journalists, who may be up on all the latest whizz-bang, bet-this-will-shock-the-reader science factoids but who have little notion of what makes science tick, what it’s all about.

One final mark of the Fantasy Scientist is lack of humility.  I have yet to see a GMO advocate who wasn’t totally sure that everything s/he believed was true and who took that “fact” as a license for swaggering arrogance directed at anyone who disagreed.  I know of no better corrective for this attitude than these wonderful words from a scientist probably greater than any alive today: Isaac Newton. 

“I do not know what I may appear to the world, but to myself I seem to have been only like a boy playing on the sea-shore, and diverting myself in now and then finding a smoother pebble or a prettier shell than ordinary, whilst the great ocean of truth lay all undiscovered before me.”

Wednesday, May 27, 2015

How to Cause Alzheimer's with Glyphosate 1: The Microbiome Route.

In my previous post I showed that the increase in Alzheimer’s disease (AD) could not be attributed solely to an increase in the elderly population (pointing to some environmental factor), and why glyphosate was a possible candidate for that factor.

But no matter how much circumstantial evidence you can produce, no account of a previously-unknown process is complete without showing a possible mechanism by which that process could be brought about.  Although there was evidence for continental drift, nobody would believe Wegener because he was unable to say how it could have happened.  Although there was evidence for the mortality of normal human cells, no-one—initially—would believe Hayflick when he said they underwent programmed death.  Hayflick was luckier than Wegener.  He lived to be able to demonstrate the function of telomeres.

At present, the cause of AD remains completely unknown.  Indeed, when I started to look at the AD literature, I was shocked to see (a) how many different possible explanations had been advanced and (b) how many of those explanations were mutually incompatible.  I would also have been shocked, if I had been as na├»ve as some GMO advocates are (or pretend to be), at (c) the failure of most papers to even mention that there were alternative explanations to theirs.  In the real world of science, hardly anyone does that; to paraphrase the immortal words of Truman Capote, “A boy has to hustle his theory”.  So the most anyone can do here is show some plausible routes by which glyphosate might cause AD.

How is glyphosate supposed to work?   According to Monsanto, “Glyphosate inhibits an enzyme that is essential to plant growth; this enzyme is not found in humans or other animals, contributing to the low risk to human health.”  That enzyme, 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase, “is the sixth enzyme on the shikimate pathway, which is essential for the synthesis of aromatic amino acids and of almost all other aromatic compounds in algae, higher plants, bacteria, and fungi”.

Bacteria?  We’re full of them!  The human gut contains more than a thousand species, so that to say, as some RoundUp labels do, that “Glyphosate targets an enzyme that is found in plants but not on people or pets” is simply false, hence the subject of a false-advertising lawsuit just opened in Los Angeles.  Indeed, they’re not just found in us, there’s a full-scale symbiosis going on—they’re a functional part of us.  According to one source, although “Mechanistic studies linking alterations in microbiota to the etiopathology of disease are relatively few”, “The human microbiome appears to modulate the regulation of multiple neurochemical pathways through a complex series of highly interactive and symbiotic host-microbiome signaling-systems that mechanistically link the gastrointestinal tract to the central nervous system, the enteric nervous system and the neuroendocrine and immune systems.”

So how could this work?  Many members of our gut microbiota have positive consequences, but some don’t.  But we don’t yet even know what all of them are, still less what they all do.  And I haven’t so far found any studies showing whether a skewed distribution of biota is found in AD patients as compared with age-matched healthy individuals, still less whether a similar skewed distribution correlates with glyphosate residues or other biomarkers of exposure to glyphosate.  “Mechanistic studies…are relatively few” is, if anything, an understatement.  And a situation that ought to be amended, pdq.

But we have an unlikely source for the likely result: chickens.

Yes, an article dealing with the effects of glyphosate on poultry gut biota shows that “the highly pathogenic bacteria as Salmonella Entritidis, Salmonella Gallinarum, Salmonella Typhimurium, Clostridium perfringens and Clostridium botulinum are highly resistant to glyphosate. However, most of beneficial bacteria as Enterococcus faecalis, Enterococcus faecium, Bacillus badius, Bifidobacterium adolescentis and Lacto-bacillus spp. were found to be moderate to highly susceptible.”  All very well, you say, but how can chickens tell you what’s going on in the human gut?  Very easily.  As its name tells you, Salmonella Gallinarum is found exclusively in chickens.  But all the other bacteria named here are found also in the human gut.  If glyphosate kills or spares them in chickens, it does exactly the same in humans.

How might changes in the balance of microbiota trigger AD?  Well, Bifidobacterium adolescentis and Lacto-bacillus species are among those susceptible to glyphosate, and “Lactobacillus, and other Bifidobacterium species, are capable of metabolizing glutamate to produce gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter in the CNS; dysfunctions in GABA-signaling are linked to anxiety, depression, defects in synaptogenesis, and cognitive impairment including AD.”  In other words, if you kill off beneficial bacteria, you can’t produce a chemical that is essential for your brain to keep running.

So that’s one route, but by no means the only possible route.  There are at least two more. But in order to discuss them, it’s necessary to know what the AD literature says about the causation of AD.  And as I said earlier, what the AD literature says is still a mess.  

But as I was preparing this, I got a very clear view of the way science works, and an equally clear view of the way the pro-GMO version of science is supposed to work.   They turn out to be very different ways.  And these two interlocking pictures, the Alzheimer’s controversy and the views of science it so clearly demarcates, will form the topic of my next post, “Real Science versus GMO Fantasy Science”.

Friday, May 22, 2015

Who’s Got the Science? An Answer to Mike and Ewan.

Before we can go further, I have to answer the multiple objections to the whole Alzheimer’s scenario raised by my two most faithful commentators, Mike W. and Ewan R. (sorry you continue to lurk behind screen names instead of putting yourselves squarely behind your remarks, but if you don’t mind the implications of that, it’s your choice).  Only when the issues they raise have been fully and thoroughly dealt with can I go on to connect the dots and show direct links between glyphosate and the mechanisms that underlie Alzheimer’s (AD).

Let’s begin with what seems at first sight the most damaging evidence: the apparent absence of any time-lag between the steep rise of glyphosate use/GE R-R crops and AD statistics.  Ewan himself inadvertently gave me the answer to that:

“Herbicide use on corn in the years prior to HT corn (1998 being year of release) 1994 - 170,221,000 lbs 1995 - 167,642,000 lbs 1996 - 186,977,000 lbs 1997 - 164,051,000 lbs 1998 - 177,012000 lbs.”  In other words, massive use of herbicides predated the emergence of glyphosate as the major herbicide.

When did I ever claim that glyphosate was the only herbicide that caused chronic disease?  Neither Swanson nor I did this.  Indeed Swanson specifically states that “We do not imply that all of these diseases have a single cause as there are many toxic substances and pathogens that can contribute to chronic disease.” We focused on glyphosate because of its present-day ubiquity, but there’s no reason to doubt that similar chemicals used in a similar way would have had similar effects.  So the steep rise in levels of AD and other chronic diseases in the 1990s reflects mostly exposure to previously-used pesticides, from 1970 (when Roundup was introduced) to the ’90s when it became dominant, giving just the predictable time-lag for AD.  After all, even industry representatives were congratulating themselves (and still do) on having substituted glyphosate (“the pesticide of the century”, as GMO advocate called it) for the more dangerous pesticides that preceded it.

As for attributing chronic diseases to obesity, that fails on a number of grounds.  For instance Hawaii, which has a shot at most-sprayed-state-in-the-union status, has a chronic kidney disease rate 30% higher than the natural average, yet in 2013 had the second-lowest incidence of obesity.  Moreover, as will be shown in subsequent posts, the mechanisms that cause obesity are the same as those involved in the etiology of chronic disease.  One thing we’ve learned (or should have) in the last few years is that the old one-size-fits-all medical model is hopelessly at variance with the facts.  People are vulnerable in different ways, simply because we all differ in our genetic make-up, so the same chemical (whether cure or poison) may have quite different effects on different people.  What effect a pesticide might have will then tend to vary from person to person, although a cascade effect is likely in some cases—pesticide-triggered hormonal dysfunctions precipitating obesity which in turn leads to diabetes, which in turn leads to AD, and so on.  But it follows too that at some stage a saturation point will be reached—only a certain proportion of the population will be likely candidates for obesity, and once that point is reached you’ll see the kind of leveling off you’d like to seize on to show that glyphosate is not what’s doing the harm.

Note that the same argument I made about the supposed “AD time-lag” applies equally to the 80’s rise in obesity that began before massive glyphosate use—other pesticides could have started what glyphosate, for all the touting of its “safety”, simply continued.  I’m not claiming that the Swanson case might not have been more effective if this point had been seen and emphasized. But obviously something in the environment started to change in the last quarter of last century.  If not pesticides, then what?  Change in lifestyles?  People don’t want to be obese.  If they did, how could the weight-loss industry be as big as it is?  How could new fad diets emerge almost daily?  You’d think all this publicity (even including TV shows like “The Biggest Loser”) would send rates plummeting. And if better diet and more exercise could cure it, you’d surely think they would.  But they don’t.  Obesity rates creep on up no matter what people do.

But there are much broader issues involved in Mike’s and Ewan’s remarks.  For instance, Ewan made a big deal of the fact that atrazine, contrary to what I suggested, is a selective pesticide.  I would have thanked him for this—no-one is readier than me to admit when I’m wrong or more grateful for any addition to my knowledge—if he had not started so immodestly crowing over it.  The fact that I got this wrong was to him a clear indication that I could not even grasp “the simple stuff” and was therefore clearly incapable when it came to “the hard stuff”.

Sorry, Ewan, that’s not how science works.  It may be how science education works, by slowly accumulating factoids into solid chunks of what currently passes for knowledge, but I suspect that’s exactly why science education in the U.S. is so ineffective.  Science isn’t like that.  First of all it advances through argument.  If you retracted from science journals all the papers that weren’t arguing one opinion against another, those journals would be two-thirds empty.  So contrary to normal practice in pro-GMO circles, you do not treat your opponents as ignorant idiots (or “fear-mongers”, if it comes to that).   Second of all, you don’t need to learn “the simple stuff” in order to learn “the hard stuff”--especially if, as in this case, the simple stuff is in one branch of science and the hard stuff is in a quite different branch.

Atrazine and its properties form part of weed science.  As I’m the first to admit, I don’t know weed science, and I’m sure Ewan does.  But weed science is just a small branch on the great tree of biology, and if you’ve been following that over the last decade or two you’ll know that there’ve been great changes—changes that produced whole new biological fields such as evo-devo and niche construction theory.  These changes have already turned biology into something a lot less friendly to the whole GMO/pesticide nexus than the “one gene = one protein = one trait”, “genes rule”, “genes are like Lego blocks” biology of the Dawkins era.  Now we know that genes are pleiotropic as well as collaborative, so that to talk about “the gene for X” where X is any behavioural trait is at best misleading.  GMO researchers had to find this out the hard way; what they seldom admit is that “implanting the gene for X” fails far more often than it succeeds.  (Occasionally even the staunchest GMO advocate can let this slip out:  “There are probably fifty different genes that have been engineered into citrus trees, most of them don't work or show little promise”—Kevin Folta.)  Far from genetic engineering being a precise and well-understood process, its procedures are just hit-and-miss trial and (mostly) error.

With the new biology we know the ease with which, especially given the ideal circumstances, resistance to any threat can evolve.  GMO enthusiasts have provided those ideal circumstances.  Ecological theory predicts that the large-scale landscape homogenization with transgenic crops will exacerbate the ecological problems already associated with monoculture agriculture.”  Artificially breed resistance to a particular herbicide in a crop, grow that crop over as large an area as possible, use that herbicide over that whole area, and you are just doing evolution’s job at a faster rate.  You are actively selecting for herbicide-resistant weeds, because you are killing off all their competition--the non-resistant weeds--and leaving a vacuum for the “superweeds” to fill (just like the asteroid strike cleared the field for us mammals 65 million years ago).  Monsanto didn’t know this—their propaganda in the nineties said there was little likelihood that glyphosate would create resistance—but anyone with up-to-date scientific knowledge could have predicted it.

Now we further know that environmental inputs can have massive effects on development from foetus to adult, modifying gene expression, upregulating or downregulating proteins, guiding not only individual development but the future evolution of species.  This new knowledge has already proved fatal to the canon on which all GMO undertakings are based—“The dose is the poison”, the dictum of a sixteenth-century alchemist/astrologer, and surely the last piece of sixteenth-century science to survive into the twenty-first century.  All pesticide safety testing is aimed at detecting acute effects, whereas the main dangers from pesticides are chronic effects that can be caused by much lower doses, but only become apparent after long periods.  (Don’t forget how they told you for years that smoking was safe, and to be sure, nobody ever collapsed as a consequence of smoking a pack.)  Chemicals can no longer be assumed to have monotonic dose-response curves, leading the Endocrine Society (who should surely know about toxicity, if anyone does) to call for a complete change is safety-testing methods.

That is what I meant and will continue to mean by the “hard stuff” that GMO advocates refuse to deal with.  I can only assume it’s because there’s no way they could.  And this explains why they have to pounce every time a GMO opponent misstates some trivial factoid about pesticides--it's the only way they can maintain the myth that they know science and the other side doesn't.  It also explains why, when I began quite recently to learn about GMOs, my first reaction was “There’s no way, in the second decade of the twenty-first century, that anyone could call this stuff scientific!”